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PROHLÍŽENÍ ABSTRAKTA

LONG-TERM LDL-APHERESIS TREATMENT AND DYNAMICS OF CIRCULATING MIRNAS IN PATIENTS WITH SEVERE FAMILIAL HYPERCHOLESTEROLEMIA
Tématický okruh: Ateroskleróza
Typ: Poster - lékařský , Číslo v programu: 312
Dlouhá D.1, Bláha M.2, Hucková P.3, Lánská V.4, Hubáček J.3, Blaha V.5

1 Centrum experimentální medicíny, Institut klinické a experimentální medicíny, Prague, 2 IV. Interní hematologická klinika, Fakultní nemocnice Hradec Králové, Hradec Králové, 3 Centrum experimentální medicíny, Institut klinické a experimentální medicíny, Praha, 4 Odbor informatiky, Institut klinické a experimentální medicíny, Praha, 5 III. interní gerontometabolická klinika, Fakultní nemocnice Hradec Králové, Hradec Králové


Background: Familial hypercholesterolemia (FH) is an autosomal-dominant disorder caused by mutations within the LDLR, APOB, and PCSK9 genes, characterized by high plasma levels of total- and low-density lipoprotein cholesterol (LDL-C). LDL apheresis (LA) serves as an extracorporeal circulation device to eliminate LDL-C from plasma. MicroRNAs (miRNAs) are important posttranscriptional gene regulators involved in the pathogenesis of atherosclerosis. Our study aimed to monitor the dynamics of twenty pre-selected circulating miRNAs in patients under long-term apheresis treatment.
Methods: Plasma samples from 12 FH patients (men=50%, age=55.3±12.2 years; mean LA overall treatment time=13.1±7.8 years) were collected before each apheresis therapy every 6th month due to the 4- years of treatment. Completely 8 follow-up (FU) samples were measured in each patient. Twenty pre-selected circulating miRNAs were measured using quantitative PCR.
Results: Dynamic changes in the relative quantity of 6 miRNAs (miR-92a, -21, -126, -122, -26a, and miR-185; all P<0.04) during follow up time were identified. Apheresis overall treatment time has influenced circulating miR-146a (P<0.04). In LDLR mutation homozygotes (N=5) compared to heterozygotes, we found higher plasma levels of miR-181, -126, -155, and miR-92a (all P<0.03). Treatment with PCSK9 inhibitors (N=6) affected plasma levels of 7 miRNAs (miR-126, -122, -26a, -155, -125a, -92a, and miR-27a; all P<0.04).
Conclusions: Long-term monitoring has shown, that LA in the patients with severe familiar hypercholesterolemia influences plasma circulating miRNAs involved in endothelial dysfunction, cholesterol homeostasis, inflammation, and plaque development. The longer is the treatment using LA the better is the miRNA milieu depicting the potential cardiovascular risk.